TrxR1 and Gpx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death

Barrera, Lawrence N., Cassidy, Aedin, Wang, Wei, Wei, Taotao, Belshaw, Nigel J., Johnson, Ian T., Brigelius-Flohe, Regina and Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370 (2012) TrxR1 and Gpx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death. BBA-Molecular Cell Research, 1823 (10). pp. 1914-1924.

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Abstract

Currently, there is significant interest in the field of diet–gene interactions and the mechanisms by which food compounds regulate gene expression to modify cancer susceptibility. From a nutrition perspective, two key components potentially exert cancer chemopreventive effects: isothiocyanates (ITCs), present in cruciferous vegetables, and selenium (Se) which, as selenocysteine, is an integral part of selenoproteins. However, the role of these compounds in the expression of key selenoenzymes once the cancer process has been initiated still needs elucidation. Therefore, this investigation examined the effect of two forms of selenium, selenium-methylselenocysteine and sodium selenite, both individually and in combination with two ITCs, sulforaphane or iberin, on the expression of the two selenoenzymes, thioredoxin reductase 1 (TrxR1) and gastrointestinal glutathione peroxidase (GPx2), which are targets of ITCs, in Caco-2 cells. Co-treatment with both ITCs and Se induced expression of TrxR1 and GPx2 more than either compound alone. Moreover, pre-treatment of cells with ITC + Se enhanced cytoprotection against H2O2-induced cell death through a ROS-dependent mechanism. Furthermore, a single and double knockdown of TrxR1 and/or GPx2 suggested that both selenoproteins were responsible for protecting against H2O2-induced cell death. Together, these data shed new light on the mechanism of interactions between ITC and Se in which translational expression of the enhanced transcripts by the former is dependent on an adequate Se supply, resulting in a cooperative antioxidant protective effect against cell death.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User: Users 2731 not found.
Date Deposited: 26 Sep 2012 08:49
Last Modified: 18 Jul 2024 23:56
URI: https://ueaeprints.uea.ac.uk/id/eprint/39674
DOI: 10.1016/j.bbamcr.2012.07.007

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